Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 200-002-3 | CAS number: 50-01-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Acute toxicity data on Guanidine hydrochloride are available for the oral, inhalation and dermal route.
The data available from three studies for the oral route all indicate LD50 values for Guanidine hydrochloride in the range between 773.6 and 1120 mg/kg bw.
The LC50 from an inhalation study for females is 3.181 mg/L air (LC50 for males = 7.655 mg/L air).
The dermal LD50 is > 2000 mg/kg bw.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1984-01-19 to 1984-02-14
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: EPA TS-792 Acute exposure, oral toxicity. Health effects test guidelines, EPA, August 1982; EPA 560/6-82-001
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Bantin Kingman, Fremont, CA
- Weight at study initiation: 150 – 255 g
- Fasting period before study: yes, over night
- Housing: individually
- Diet (e.g. ad libitum): Certified Purina Rodent Chow Diet 5062, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 11 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.2°C to 25°C
- Humidity (%): 40 to 53%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): 0.74-1.02 mL/animal in males, 0.59-0.74 mL/animal in females
- Justification for choice of vehicle: test substance is soluble in water - Doses:
- 0, 278, 360, 464, 600, 775 mg/kg bw (expressed as active ingredient Guanidine), corresponding to 0, 453.14, 756.32, 978, 1263.25 mg/kg bw Guanidine hydrochloride
- No. of animals per sex per dose:
- 9 in treated groups; 5 in vehicle control and cage control
- Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs, mortality: after 2 and 4 h, daily thereafter
Body weight: twice weekly
- Necropsy of survivors performed: yes; completet gross necropsy
- Other examinations performed: histopathology of CNS for animals with neurological symptoms - Statistics:
- Probit analysis
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 556.5 mg/kg bw
- Based on:
- other: Guanidine
- 95% CL:
- 492.3 - 630.9
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 474.6 mg/kg bw
- Based on:
- other: Guanidine
- 95% CL:
- 402 - 562.7
- Key result
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 907.1 mg/kg bw
- Based on:
- test mat.
- Remarks:
- Guanidine hydrochloride
- 95% CL:
- 802.45 - 1 028.4
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 773.6 mg/kg bw
- Based on:
- test mat.
- Remarks:
- Guanidine hydrochloride
- 95% CL:
- 655.3 - 917.2
- Mortality:
- - vehicle control: 0/5 males, 0/5 females died
- cage control: 0/5 males, 0/5 females died
- 278 mg/kg bw: 0/9 males, 0/8 females died
- 360 mg/kg bw: 0/9 males, 2/8 females died
- 464 mg/kg bw: 2/9 males, 5/9 females died
- 600 mg/kg bw: 5/9 males, 4/7 females died
- 775 mg/kg bw: 9/9 males, 9/9 females died
(reduced total numbers are due to misdosing; those animals were removed from the study) - Clinical signs:
- other: most frequent clinical signs: - central nervous system-neuromuscular disturbances at all dose groups( 80 of 86 animals) - increased startle reflex, hyperactivity, and disorientation up to 464 mg/kg bw, recovery within one week - in the two higher dose gr
- Gross pathology:
- - no test compound-related lesions in the CNS (gross and light microscopic examination)
- the only test compound-related findings were in the gastrointestinal tract (black/serosanguinous material in the stomach, focal depression in the glandular mucosa of the stomach, black and diffuse red areas in the glandular mucosa of the stomach, black and tarry material in the intestine, black and tarry feces)
- in surviving animals no test compound-related gross lesions were reported; 2 male and 1 female rats had a unilateral dilated renal pelvis, which is considered incidential - Other findings:
- - Histopathology:
Several rats exhibited central nervous system (CNS) signs. Some rats that exhibited CNS signs died and some others survived. The cerebrum, brainstem and cerebellum of 4 animals died were examined by light microscopy and no lesions were observed. - Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The oral LD50 for Guanidine hydrochloride in rats was 907.1 mg/kg bw (95% c.i. 802.45 - 1028.4) in males and 773.6 mg/kg bw (95% c.i 655.3 - 917.2) in females. Thus, Guanidine hydrochloride has to be classified for Acute oral toxicity, Category 4.
- Executive summary:
In an acute oral toxicity study similar to OECD guideline 401, groups of fasted Sprague-Dawley rats (9/sex) were given a single oral dose of Guanidine hydrochloride (>98% purity, 61.8% base equivalent Guanidine) in water at doses of 0, 278, 360, 464, 600 and 775 mg/kg bw (expressed as Guanidine base), corresponding to 0, 453.14, 756.32, 978, 1263.25 mg/kg bw Guanidine hydrochloride and observed for 14 days.
No mortality occurred in the lowest dose group. 0/9 males, 2/8 females in the 360 mg/kg bw dose group died; 2/9 males, 5/9 females in the 464 mg/kg bw dose group; 5/9 males, 4/7 females in the 600 mg/kg bw dose group and 9/9 males, 9/9 females in the 775 mg/kg bw dose group. Reduced total numbers are due to misdosing; those animals were removed from the study.
Clinical signs were observed in the CNS (increased startle reflex, hyperactivity, and disorientation) and in the gastro-intestinal tract (hunched posture, increased salivation with some staining of the muzzle, and diarrhea) in all dose groups. However, there were no microscopic findings in cerebrum, brainstem and cerebellum of animals with CNS symptoms.
Gross pathology revealed black/serosanguinous material in the stomach, focal depression in the glandular mucosa of the stomach, black and diffuse red areas in the glandular mucosa of the stomach, black and tarry material in the intestine, black and tarry feces.
In the surviving animals no test compound-related gross lesions were reported.
Several rats exhibited central nervous system (CNS) signs. Some rats that exhibited CNS signs died and some others survived. The cerebrum, brainstem and cerebellum of 4 animals died were examined by light microscopy and no lesions were observed.
Oral LD50 Males = 556.5 mg Guanidine/kg bw (95% C.I. 492.3 - 630.9 mg/kg bw)
Oral LD50 Females = 474.6 mg Guanidine/kg bw (95% C.I. 402 - 562.7 mg/kg bw)
corresponding to:
Oral LD50 males = 907.1 mg/kg bw (95% c.i. 802.45 - 1028.4) Guanidine hydrochloride
Oral LD50 females = 773.6 mg/kg bw (95% c.i 655.3 - 917.2) Guanidine hydrochloride
Thus, Based on these data, Guanidine hydrochloride has to be classified for Acute toxicity, Category 4.
Reference
Sex Endpoint Effect level 95% CL
male LD10 441.8 mg/kg bw (Guanidine base) 326.3 — 497.9
female LD10 321.4 mg/kg bw (Guanidine base) 209.1 — 383.9
male LD90 701.1 mg/kg bw (Guanidine base) 621.1 — 956
female LD90 700.8 mg/kg bw (Guanidine base) 584.8 — 1089.9
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 773.6 mg/kg bw
- Quality of whole database:
- The available studies are guideline-conform and of high quality (key study: RL1, supporting studies RL2).
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Age at study initiation: 6 to 8 weeks old
- Weight at study initiation: 140 - 200 g
- Fasting period before study: no data
- Housing: groups of 5 animals by sex in grid-floor stainless steel cages
- Diet (e.g. ad libitum): ad libitum; SQC Rat and Mouse Maintenance Diet No. 1 Expanded, Special Diets Services Ltd. Witham
- Water (e.g. ad libitum): ad libitum; mains water
- Acclimation period: 25 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C):19 - 25 °C
- Humidity (%): 40 - 70 %
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- head only
- Vehicle:
- clean air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical anodised aluminium exposure chamber
- Exposure chamber volume: 30 L
- Method of holding animals in test chamber: head-only
- Source and rate of air: The compressed air supply used was from a clean dry filtered source.
- Method of conditioning air: -
- System of generating particulates/aerosols: DeVilbiss model 646 liquid nebulizer generator, dynamic (continuous flow)
- Method of particle size determination: The particle size was determined using a Delron C55 Cascade Impactor, with 5 separation
stages corresponding to maximum mass median aerodynamic diameters of 0.5, 1.0. 2.0. 4.0 and 8 µm. The samples were obtained
hourly, over periods of up to 8 minutes, -during the exposure period.
- Treatment of exhaust air: The atmospheres were filtered, exhausted to the outside of the building and vented.
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure
chamber were measured continuously and recorded at hourly interva1s throughout th'e 4-hour exposure peri od, using a
digital thermometer with remote probe located in the chamber and a paper hygrometer located in the exhaust duct of the chamber.
TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of the test article was determined gravimetrically. The atmosphere
was sampled by drawing a known volume through an open face glass fibre filter positioned at a site representative of that
occupied by the external nares of the experimental animals.
- Samples taken from breathing zone: yes
TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- 0.513, 2.118, 4.585 and 6.518 mg/L
- No. of animals per sex per dose:
- 5 aminals per sex per group
- Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice daily for dead or moribund. The body weight of each animal was recorded immediately before and
after exposure, on days 8 and 15 of the study and at necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Clinical signs were observed at hourly intervals during the exposure period, then for the remainder of the working day, and once daily thereafter for
14 days.
Necropsy: A full internal and external examination was made under the general supervision of a pathologist. The nasal passages were examined and
an assessment made of any irritation of the respiratory tract.
Organ weights: The lungs, bronchi and trachea were dissected free from fat and other contiguous tissue and weighed together.
Histology: Samples of all gross lesions were fixed in 10% neutral buffered formalin and retained without further processing. - Statistics:
- The median lethal concentrations (LC50) together·with 95% fiducial limits were calculated separately for males and females, and for
sexes combined, from the recorded mortality rate using a probit analysis method (Finney, D.J. (971)
Probit Analysis, 3rd ed., Cambridge University Press).
,I
,I - Sex:
- female
- Dose descriptor:
- LC50
- Effect level:
- 3.181 mg/L air (analytical)
- Based on:
- test mat.
- 95% CL:
- 0.567 - 50.411
- Exp. duration:
- 4 h
- Sex:
- male
- Dose descriptor:
- LC50
- Effect level:
- 7.655 mg/L air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 5.319 mg/L air (analytical)
- Based on:
- test mat.
- 95% CL:
- 2.981 - 34.296
- Exp. duration:
- 4 h
- Mortality:
- Qveral-l there was a positive correlation between mortality and chamber concentration. As the minimum level at which death
occurred was 4.585 mg/l for males and 2.118 mg/l for females, the possibility of a sex difference cannot be eliminated.
One male in group 5 died during exposure. Except for one death on day four all deaths occurred on days one or two of the study.
Seven animals were killed for humane reasons on day one. Five of these decedents were in moribund condition. - Clinical signs:
- other: Marked signs of toxicity were observed at 4.585 and 6.518 mg/L immediately after exposure. The signs included ataxia, occasionally prostration and irregular respiration. and convulsion and signs of ejaculation at 4.585 mg/l. During and/or following expos
- Body weight:
- Body weight losses occurred as a result of the r~straint procedures in test and control groups. The losses tended to be greater in
treated groups and persisted in a few individuals until day 8 of the study. However, overall there was no marked effect on body
weight. - Gross pathology:
- Mean absolute and relative lung weights at termination for treated groups tended to be slightly higher than the corresponding control va1ues. but all values fell withi n the normal range and the numerical differences were too small to conclude there was a treatment-related effect.
Occasional lung weights for decedents were near or ablove the upper limits of the normal range.
This was probably due to agonal congestive changes.
Animals surviving to termination showed only incidental changes. Some decedents were unremarkable but others had discoloured and
inflated lungs suggestive of acute effects on the cardiopulmonary system. Four of the flve group 3 females had sore forefeet
possible due to self-inflicted trauma. - Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- Based on the LC50 female of 3.181 mg/L air the test substance has to be classified according to CLP, EU GHS (Regulation (EC) No. 1272/2008) in Toxicity Category IV.
- Executive summary:
In an acute inhalation toxicity study performed according to OECD Guideline 403 5 young Sprague-Dawley rats per sex per group were exposed at single chamber concentrations of 0.513, 2.118, 4.585 and 6.518 mg/L of Guanidine hydrochloride (98.5 % a.i.) by inhalation (head-only) over a period of 4 hours. Corresponding nominal concentrations were in the range 2.124 to 15.280 mg/L. The mass median aerodynamic diameters of the particles in the atmospheres fell in the range 1.88 to 5.62 µm. The aerosol for animal exposures was prepared from an aqueous solution of the test article. A similar group of 5 males and 5 females was exposed to filtered air as a control. Animals then were observed for 14 days.
The acute inhalation median lethal concentrations, calculated by a probit method, were:
LC50 combined: 5.319 mg/L
LC50 Males: 7.655 mg/L
LC50 Females: 3.181 mg/L
Deaths occurred in males at a level of 4.585 mg/l and above, and in females at a level of 2.118 mg/l and above. Overall there was a dose-related relationship between mortality and chamber concentration. Nearly all deaths occurred on days one or two of the study. Marked clinical signs were first observed on the day of exposure. The signs included ataxia and occasionally prostration, irregular respiration, convulsion and signs of ejaculation. A few individuals showed body weight loss that persisted one week after treatment, but overall there was no marked treatment related effect on body weight.
There was no evidence of a treatment-related, effect on lung weight in survivors. Occasional increases in lung weights in decedents were probably due to agonal congestive changes. Animals surviving to termination were unremarkable macroscopically. A few decedents had discolored and inflated lungs.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 3 181 mg/m³ air
- Quality of whole database:
- The key study is GLP compliant and of high quality (RL 1).
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1984-05-18 to 1984-08-01
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods
- Qualifier:
- according to guideline
- Guideline:
- other: EPA TS-792 Acute exposure, dermal toxicity. Health effects test guidelines, EPA, August 1982; EPA 560/6-82-001
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Elkhorn Rabbitry, 5265 Starr Way, Watsonville, CA 95076
- Age at study initiation: young adults
- Weight at study initiation: 2.8 to 3.7 kg
- Housing: individually
- Diet (e.g. ad libitum): 150 g of Certified Purina Chow Diet 5322
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 25 d (quarantine, acclimation)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 24°C
- Humidity (%): 46 to 74%, except for spikes up to 94% during cleaning
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- occlusive
- Vehicle:
- physiological saline
- Details on dermal exposure:
- TEST SITE
- Area of exposure: 240 cm²
the substance was applied on gauze dressing, taped with hypoallergenic tape (Durapore) and wrapped with bandage (Vetrap)
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: after 24 h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: yes, 0.9% saline - Duration of exposure:
- 24 h
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs and mortality daily; dermal reactions 0.5, 24, 48, 74 h after removal of the patches; body weights were recorded 7 times during test period
- Necropsy of survivors performed: yes
- Other examinations performed: skin from exposed area was examined microscopically - Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- no mortality occurred
- Clinical signs:
- other: systemic: - no substance-related clinical signs local (dermal): - erythema was observed in all rabbits 30 min after patch removal; 24 h after patch removal the erythema had disappeared in five animals - slight erythema, necrosis and ulceration was observ
- Gross pathology:
- - epidermal ulceration covered by a fibrinocellular exudate in one male with necrosis and eschar formation
- no other gross findings - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The dermal LD50 of Guanidine hydrochloride in rabbits was > 2000 mg/kg bw.
- Executive summary:
In an acute dermal toxicity study similar to OECD guideline 402 groups of 5 young adult New Zealand White rabbits/sex were dermally exposed to Guanidine hydrochloride (98% pure) moistened with 0.9% saline for 24 h to 240 cm² body surface area at a limit dose of 2000 mg/kg bw using occlusive dressing. Animals then were observed for 14 days.
No mortality occurred. No substance-related systemic effects were observed. Exposure to the test substance caused dermal irritation and eschar formation.
Dermal LD50 > 2000 mg/kg bw.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- The key study is GLP compliant and of high quality (RL 1).
Additional information
Acute toxicity data on Guanidine hydrochloride are available for the oral, inhalation and dermal route.
Acute oral toxicity
In an acute oral toxicity study similar to OECD guideline 401, groups of fasted Sprague-Dawley rats (9/sex) were given a single oral dose of Guanidine hydrochloride (>98% purity, 61.8% base equivalent Guanidine) in water at doses of 0, 278, 360, 464, 600 and 775 mg/kg bw (expressed as active ingredient Guanidine base), corresponding to 0, 453.14, 756.32, 978, 1263.25 mg/kg bw Guanidine hydrochloride and observed for 14 days.
No mortality occurred in the lowest dose group. 0/9 males, 2/8 females in the 360 mg/kg bw dose group died; 2/9 males, 5/9 females in the 464 mg/kg bw dose group; 5/9 males, 4/7 females in the 600 mg/kg bw dose group and 9/9 males, 9/9 females in the 775 mg/kg bw dose group. Reduced total numbers are due to misdosing; those animals were removed from the study.
Clinical signs were observed in the CNS (increased startle reflex, hyperactivity, and disorientation) and in the gastro-intestinal tract (hunched posture, increased salivation with some staining of the muzzle, and diarrhea) in all dose groups. However, there were no microscopic findings in cerebrum, brainstem and cerebellum of animals with CNS symptoms.
Gross pathology revealed black/serosanguinous material in the stomach, focal depression in the glandular mucosa of the stomach, black and diffuse red areas in the glandular mucosa of the stomach, black and tarry material in the intestine, black and tarry feces.
In the surviving animals no test compound-related gross lesions were reported.
Several rats exhibited central nervous system (CNS) signs. Some rats that exhibited CNS signs died and some others survived. The cerebrum, brainstem and cerebellum of 4 animals died were examined by light microscopy and no lesions were observed.
Oral LD50 Males = 556.5 mg Guanidine/kg bw (95% C.I. 492.3 - 630.9 mg/kg bw)
Oral LD50 Females = 474.6 mg Guanidine/kg bw (95% C.I. 402 - 562.7 mg/kg bw)
corresponding to:
LD50 males = 907.1 mg/kg bw (95% c.i. 802.45 - 1028.4)
LD50 females = 773.6 mg/kg bw (95% c.i 655.3 - 917.2) expressed as Guanidine hydrochloride.
This is supported by two further oral toxicity studies with Guanidine hydrochloride in mice and rats, respectively:
The oral LD50 for Guanidine base in mice was 570.8 mg/kg bw (95% c.i. 491 - 694 mg/kg bw) in males and 612 mg/kg bw (95% c.i. 492 – 1183 mg/kg bw) in females, corresponding to 930.4 mg/kg bw (95% c.i. 800.33 - 1131.22 mg/kg bw) in males and 997.56 mg/kg bw (95% c.i. 801.96 - 1928.29 mg/kg bw) in females expressed as Guanidine hydrochloride.
The oral LD50 for Guanidine hydrochloride in rats was 1120 mg/kg bw (95% c.i. 991 – 1266 mg/kg bw).
Acute inhalation toxicity
In an acute inhalation toxicity study performed according to OECD Guideline 403, 5 young Sprague-Dawley rats per sex per group were exposed at single chamber concentrations of 0.513, 2.118, 4.585 and 6.518 mg/L of Guanidine hydrochloride (98.5 % a.i.) by inhalation (head-only) over a period of 4 hours. Corresponding nominal concentrations were in the range 2.124 to 15.280 mg/L. The mass median aerodynamic diameters of the particles in the atmospheres fell in the range 1.88 to 5.62 µm. The aerosol for animal exposures was prepared from an aqueous solution of the test article. A similar group of 5 males and 5 females was exposed to filtered air as a control. Animals then were observed for 14 days.
The acute inhalation median lethal concentrations, calculated by a probit method, were:
LC50 combined: 5.319 mg/L (5319 mg/m³)
LC50 Males: 7.655 mg/L (7655 mg/m³)
LC50 Females: 3.181 mg/L (3181 mg/m³)
Deaths occurred in males at a level of 4.585 mg/L and above, and in females at a level of 2.118 mg/L and above. Overall there was a dose-related relationship between mortality and chamber concentration. Nearly all deaths occurred on days one or two of the study. Marked clinical signs were first observed on the day of exposure. The signs included ataxia and occasionally prostration, irregular respiration, convulsion and signs of ejaculation. A few individuals showed body weight loss that persisted one week after treatment, but overall there was no marked treatment related effect on body weight.
There was no evidence of a treatment-related, effect on lung weight in survivors. Occasional increases in lung weights in decedents were probably due to agonal congestive changes. Animals surviving to termination were unremarkable macroscopically. A few decedents had discoloured and inflated lungs.
Acute dermal toxicity
In an acute dermal toxicity study similar to OECD guideline 402 groups of 5 young adult New Zealand White rabbits/sex were dermally exposed to Guanidine hydrochloride (98% pure) moistened with 0.9% saline for 24 h to 240 cm² body surface area at a limit dose of 2000 mg/kg bw using occlusive dressing. Animals then were observed for 14 days.
No mortality occurred. No substance-related systemic effects were observed. Exposure to the test substance caused dermal irritation and eschar formation.
Dermal LD50 > 2000 mg/kg bw Guanidine hydrochloride.
Justification for classification or non-classification
According to CLP, EU GHS (Regulation (EC) No 1272/2008), Guanidine hydrochloride is classified with Hazard Category 4 for acute oral toxicity (harmful if swallowed) since the results obtained in all available studies are conclusive, and LD50 values are in the range from 773.6 to 1120 mg/kg bw.
The findings from acute oral toxicity studies suggest that the guanidine ion exhibits primary effects on the central nervous system / neuromuscular system. However, effects were observed in the range of classification Hazard Category 4, therefore on the basis of available data no additional classification for STOT-SE is considered necessary.
Guanidine hydrochloride is classified for acute inhalation toxicity (harmful if inhaled) with Hazard Category 4 since the lowest obtained LC50 from an acute inhalation study was 3.181 mg/L for female rats.
Guanidine hydrochloride is not classified for acute dermal toxicity since the LD50 value is > 2000 mg/kg bw.
Guanidine hydrochloride is labelled with R20/22 according to Directive 67/548 EEC. According to CLP, EU GHS (Regulation (EC) No 1272/2008), labelling with H302/332 is required.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.